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PDCD10-Deficient Tumor Cells Reprogram Angiogenesis Through Paracrine Endothelial Activation and GSC-like Plasticity in GBM.

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Τίτλος: PDCD10-Deficient Tumor Cells Reprogram Angiogenesis Through Paracrine Endothelial Activation and GSC-like Plasticity in GBM.
Συγγραφείς: Chen ZR; Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.; Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany., Chen Z; Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.; Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany., Wan XY; Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.; Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany., Busch MA; Department of Neuroanatomy, Medical Faculty, Institute of Anatomy II, University of Duisburg-Essen, 45147 Essen, Germany., Dünker N; Department of Neuroanatomy, Medical Faculty, Institute of Anatomy II, University of Duisburg-Essen, 45147 Essen, Germany., Rauschenbach L; Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.; Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany., Sure U; Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.; Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany., Zhu Y; Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.; Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.
Πηγή: Cells [Cells] 2026 Aug 25; Vol. 15 (17). Date of Electronic Publication: 2026 Aug 25.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE
Imprint Name(s): Original Publication: Basel, Switzerland : MDPI
Ιατρικοί όροι (MeSH): Neovascularization, Pathologic*/metabolism , Neovascularization, Pathologic*/pathology , Glioblastoma*/pathology , Glioblastoma*/metabolism , Glioblastoma*/blood supply , Glioblastoma*/genetics , Apoptosis Regulatory Proteins*/metabolism , Apoptosis Regulatory Proteins*/deficiency , Apoptosis Regulatory Proteins*/genetics , Neoplastic Stem Cells*/pathology , Neoplastic Stem Cells*/metabolism , Brain Neoplasms*/pathology , Brain Neoplasms*/metabolism , Brain Neoplasms*/blood supply , Endothelial Cells*/metabolism , Endothelial Cells*/pathology , Paracrine Communication* , Cell Plasticity*, Culture Media, Conditioned/pharmacology ; Humans ; Animals ; Cell Line, Tumor ; Kruppel-Like Factor 4 ; Mice ; Membrane Proteins ; Proto-Oncogene Proteins
Περίληψη: Glioblastoma (GBM) is characterized by extensive neo-angiogenesis, which drives rapid tumor growth and therapeutic resistance. We previously identified PDCD10 as a tumor suppressor in GBM. Here, we investigated whether PDCD10 loss promotes neo-angiogenesis through paracrine signaling and GBM cell plasticity. PDCD10 knockdown (shPDCD10) enhanced endothelial angiogenic activity after treatment with conditioned medium (CM) from shPDCD10 cells and in a direct co-culture model. Moreover, application of CM to the chicken chorioallantoic membrane increased vascular branching in an in vivo angiogenesis model. Antibody array analysis detected elevated levels of multiple pro-angiogenic factors following PDCD10 depletion. In a GBM mouse model, shPDCD10 tumors exhibited pronounced hypervascularity and stromal expansion. Indeed, immunofluorescence revealed colocalization of CD31 with the tumor cell reporter RFP in a subset of implanted shPDCD10 GBM cells, suggesting that these tumor cells acquired an endothelial molecular signature. PDCD10 loss also promoted a glioma stem cell (GSC)-like phenotype, characterized by enhanced clonogenicity, sphere formation, and upregulation of Nestin, KLF4, and SOX2. Under endothelial induction conditions, shPDCD10 sphere-derived cells exhibited endothelial-like characters, showing greater tube-forming capacity and increased Ac-LDL uptake. Taken together, these findings demonstrate that PDCD10 loss promotes GBM neo-angiogenesis involving complementary paracrine and GSC-like plasticity mechanisms, highlighting PDCD10 as a potential therapeutic target to suppress neo-angiogenesis in GBM.
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Grant Information: IFORES D/107 Essen University Hospital
Contributed Indexing: Keywords: angiogenesis; cell plasticity; glioblastoma; glioma stem cells; programmed cell death 10; tumor-derived endothelial cell
Substance Nomenclature: 0 (Apoptosis Regulatory Proteins)
0 (Kruppel-Like Factor 4)
0 (PDCD10 protein, human)
0 (KLF4 protein, human)
0 (Klf4 protein, mouse)
0 (Culture Media, Conditioned)
0 (Membrane Proteins)
0 (Proto-Oncogene Proteins)
Entry Date(s): Date Created: 20260915 Date Completed: 20260915 Latest Revision: 20260916
Update Code: 20260916
PubMed Central ID: PMC13565472
DOI: 10.3390/cells15171532
PMID: 42738826
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2073-4409
DOI:10.3390/cells15171532